The overall objectives of this proposal are to understand the mechanisms of long-term synaptic plasticity. Long-term synaptic plasticity is widely believed to underlie learning and memory, and understanding the mechanisms of this plasticity will yield insight into the normal development and function of the brain as well as the pathology resulting from a wide range of neurological diseases. This proposal will utilize the technique of recording from individual pairs of synaptically connected neurons. This approach allows much better resolution of the different plastic states a synapse may exhibit than is afforded by many previous studies of plasticity that are based on summed measurements of many synaptic connections. Specifically, we will examine how the state of a synapse and the history of states a synapse has visited influence its potential to exhibit plasticity. We will determine if there are differences in the ability of synapse to be potentiated based on its history of being in active or silent states. We will also examine how different glutamate receptor components of the synaptic response are changed during potentiation of synapses that start in different states [unreadable] [unreadable]